In the central nervous system (CNS) the transmission of stimuli takes place by the interaction of a neurotransmitter, released by a neuron, with a neuroreceptor.
L-glutamic acid (glutamate), the most commonly occurring neurotransmitter in the CNS, plays a critical role in a large number of physiological processes. The glutamate-dependent stimulus receptors are divided into two main groups. The first main group forms ligand-controlled ion channels. The second main group forms G-protein-coupled receptors, and includes the metabotropic glutamate receptors (mGluR).
At present eight different members of these mGluR are known and of these some even have sub-types. On the basis of structural parameters, their different influences on the synthesis of secondary metabolites and their different affinity to low-molecular weight chemical compounds, these eight receptors can be sub-divided into three sub-groups: mGluR1 and mGluR5 belong to group I, mGluR2 and mGluR3 belong to group II and mGluR4, mGluR6, mGluR7 and mGluR8 belong to group III.
Metabotropic glutamate receptors belonging to the second group can be used for the treatment or prevention of diseases and conditions related to the functioning of the mGluR. These include acute and/or chronic neurological disorders such as restricted brain function caused by bypass operations or transplants, poor blood supply to the brain, spinal cord injuries, head injuries, hypoxia caused by pregnancy, cardiac arrest and hypoglycaemia. Other treatable indications in this connection are Alzheimer's disease, Huntington's chorea, amyotrophic lateral sclerosis (ALS), dementia caused by AIDS, eye injuries, retinopathy, cognitive disorders, idiopathic parkinsonism or parkinsonism caused by medicaments as well as conditions which lead to glutamate-deficiency conditions, such as muscle spasms, convulsions, migraine, urinary incontinence, nicotine addiction, psychoses, opiate addiction, anxiety, vomiting, chronic pain, dyskinesia, depressions and pains (see for example EP 807 621 and EP 696 577).